Table of Contents

Volume 5, Issue 3

  March 2009

  Pages 113 - 189

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 Issue Catalogue (MARC XML)

EDITOR'S CORNER

Open Access Article

Letter from the Editor

Ronald W. Ellis and Eva Maria Riedmann
Page 113
http://dx.doi.org/10.4161/hv.5.3.8257
PDF




PORTRAIT OF A LEADING VACCINOLOGIST

Open Access Article

From clinical research to vaccination policy: 25 years experience in vaccinology

Luc Hessel
Pages 114 - 118
http://dx.doi.org/10.4161/hv.5.3.8153
PDF




MEETING REPORT

Open Access Article

AIDS Vaccine 2008 Conference

Galit Alter, Jintanat Ananworanich, Ralph Pantophlet, Ed P. Rybicki and Luigi Buonaguro
Pages 119 - 125
http://dx.doi.org/10.4161/hv.5.3.7557
Abstract | PDF

The “AIDS Vaccine 2008” Conference was held in Cape Town, South Africa (October 13 to 16, 2008) and organized, under the aegis of the Global HIV Vaccine Enterprise, by Dr Lynn Morris (Chair of the Conference) from Natl. Inst. Communicable Dis., Univ. Witwatersrand, Johannesburg; Dr Koleka Mlisana from CAPRISA, Univ. KwaZulu-Natal, Durban, Dr Glenda Gray from Perinatal HIV Research Unit, Univ. Witwatersrand, Johannesburg and Dr Carolyn Williamson from Inst. Infect. Dis. and Mol. Medicine, UCT, Cape Town (Co-Chairs of the Conference).


Since the first AIDS Vaccine conference, organized in Paris in 2000, this was the first time it was held outside of the U.S. and Europe, and involved nearly 1000 participants.


Besides 3 Plenary Sessions with 10 state-of-the-art plenary lectures and 1 Keynote Lecture given by Dr. A.S. Fauci (Director of NIAID, NIH, USA), the Conference was organized in 9 oral sessions, 4 poster discussion groups covering a wide spectrum of scientific information relating to HIV vaccine research and development. Moreover 3 Symposia, 2 Special Sessions, 1 Roundtable as well as 2 Debates were held, the latter focusing on current controversial topics.


The conference opening was memorable for a number of reasons: among these was the presence of South Africa’s new Minister of Health, Barbara Hogan who, in her first speech in a major forum as a senior member of the SA Government, affirmed that HIV causes AIDS, and that the search for a vaccine is of paramount importance to SA and the rest of the world.


A scientific summary of the Conference is reported in the present article, divided into 4 major topics: (1) vaccine concepts and design; (2) T-cell immunology and innate immunity; (3) B-cell immunology, neutralizing antibodies and mucosal immunology and (4) clinical trials.




REVIEWS

Open Access Article

Vaccination strategies and vaccine formulations for epidemic and pandemic influenza control

Joost H.C.M. Kreijtz, Albert D.M.E. Osterhaus and Guus F. Rimmelzwaan
Pages 126 - 135
http://dx.doi.org/10.4161/hv.5.3.6986
Abstract | PDF

Influenza viruses of the H5N1 subtype cause an ever-increasing number of bird-to-human transmissions and a pandemic outbreak caused by these viruses is imminent. Therefore, the availability of safe and effective vaccines is highly desirable and their development considered a priority. However, using production and use of seasonal influenza vaccine as template for the production of pandemic H5N1 vaccines did not yield effective vaccines. High antigen doses were required to induce appreciable antibody responses. In addition, limited production capacity and long production times are other disadvantages of conventional influenza vaccine preparations. Here, we review recent developments that will contribute to a more rapid availability of sufficient doses of highly efficacious and safe pandemic influenza vaccines. The new developments include the establishment of novel methods to prepare vaccine strains, novel production technologies and the use of novel adjuvants and alternative vaccine formulations.

Open Access Article

The effect of active immunization on varicella-related hospitalizations in Israel

Liat Lerner-Geva, Galit Hirsh-Yechezkel, Ilia Novikov, Hagit Farkash, Valentina Boyko, Zvi Spirer and Justen H. Passwell
Pages 136 - 140
http://dx.doi.org/10.4161/hv.5.3.6811
Abstract | PDF

The purpose of this study is to report on the impact of introduction of the varicella vaccine “Varilix” on hospitalizations due to varicella, following licensure in Israel in June, 2000. Data on children hospitalized throughout Israel with the diagnosis of varicella were collected from 1998 until 2003. The national rate of varicella-related hospitalizations decreased during the period 2001-2002. However in 2003 an increase in hospitalization occurred. Based on an assumption that at least 22,000 vaccinations per year were administered, we estimate that there is a greater than 60% reduction in the risk for hospitalization in the immunized population (RR=0.32; 0.10-1.00). In summary, no national trend in reduction of hospitalization has yet been observed, but a significant reduction in hospitalization is apparent for vaccinated children.




RESEARCH PAPERS

Open Access Article

Enhanced in vivo immunogenicity of SIV vaccine candidates with cationic liposome-DNA complexes in a rhesus macaque pilot study

Jeff Fairman, Joseph Moore, Mathieu Lemieux, Koen Van Rompay, Yongzhi Geng, John Warner and Kristina Abel
Pages 141 - 150
http://dx.doi.org/10.4161/hv.5.3.6589
Abstract | PDF

This pilot study tested the immunogenicity of a novel cationic liposome-DNA complex (CLDC) immunomodulatory vaccine adjuvant. Combined with a specific antigen, CLDC enhanced anti-SIV immune responses induced by various SIV vaccine candidates. Rhesus macaques immunized in the presence of CLDC developed stronger SIV-specific T and B cell responses compared to animals immunized without CLDC. These differences persisted and resulted in better memory responses after an in-vivo boost of the animals several months later with whole AT-2 inactivated SIVmac239. Thus, CLDC should be explored further as a potential immunomodulatory adjuvant in HIV vaccine design.

Open Access Article

Priming of CD4+ and CD8+ T cell responses using a HCV core ISCOMATRIX™ vaccine: A phase I study in healthy volunteers

Debbie Drane, Eugene Maraskovsky, Rebecca Gibson, Sue Mitchell, Megan Barnden, Alan Moskwa, David Shaw, Barbara Gervase, Stephen Coates, Michael Houghton and Russell Basser
Pages 151 - 157
http://dx.doi.org/10.4161/hv.5.3.6614
Abstract | PDF

The disease burden and public health impact of chronic HCV infection continues to be a major problem globally. Current treatment for chronic HCV infection is not effective in all patients and is frequently associated with unacceptable side effects. Clearly a need exists for improved treatments and one such strategy is the use of therapeutic vaccines. Although still not completely understood, emerging data indicate that the generation of CD4+ and CD8+ T cells are important for the clearance of HCV. We have developed a prototype vaccine with the HCV Core protein and ISCOMATRIX™ adjuvant (HCV Core ISCOMATRIX™ vaccine). ISCOMATRIX™ vaccines have been shown to induce CD4+ and CD8+ T cell responses to a range of antigens in both animal models and in human studies. Additionally, ISCOMATRIX™ vaccines have been shown to be safe and generally well tolerated in several clinical trials. Preliminary studies demonstrated that the prototype HCV Core ISCOMATRIX™ vaccine induced strong CD4+ and CD8+ T cell responses in monkeys following immunisation. Here we show the results of a Phase I placebo controlled, dose escalation clinical study designed to evaluate the safety, tolerability and immunogenicity of the HCV Core ISCOMATRIX™ vaccine in healthy individuals. The 30 subjects received 3 immunisations of HCV Core ISCOMATRIX™ vaccines or placebo vaccine on days 0, 28 and 56. The HCV Core ISCOMATRIX™ vaccines contained 5, 20 or 50 μg HCV Core protein with 120 μg ISCOMATRIX™ adjuvant. The adverse events reported were generally mild to moderate in severity, of short duration and self-limiting. The most common adverse events were injection site reactions such as pain and redness as well as myalgia. Antibody responses were detected in all but one of the participants receiving the HCV Core ISCOMATRIX™ vaccine and there was no indication of a dose response. CD8+ T cell responses were only detected in 2 of the 8 participants receiving the highest dose. T cell cytokines were detected in 7 of the 8 participants in the highest dose group. The results of this study support the further evaluation of this prototype HCV Core ISCOMATRIX™ vaccine in HCV infected subjects.

Open Access Article

HER1-ECD vaccination dispenses with emulsification to elicit HER1-specific anti-proliferative effects

Yeranddy Aguiar Alpízar, Belinda Sánchez Ramírez, Diana Rosa Hernández Fernández, Ailem Rabasa Capote, Greta Garrido Hidalgo, Rolando Pérez Rodríguez and Luis Enrique Fernández Molina
Pages 158 - 165
http://dx.doi.org/10.4161/hv.5.3.7129
Abstract | PDF

EGFR (HER1) highlights as one of the most relevant tumour associated antigen in epithelial malignant cells. Monoclonal antibodies and tyrosine kinase inhibitors against EGFR remain as the most advanced approaches in clinical trials. More recently, an active immunotherapy using the HER1 extracellular domain (ECD) adjuvated in very small sized proteoliposomes (VSSP) and emulsified in Montanide ISA-51 demonstrated its strength to inhibit tumor cell line proliferation by arresting cells in G₀/G₁ stage and induction of apoptosis. In this study, we present a simpler HER1-ECD-based formulation, which is lacking the oily component Montanide ISA-51. Generated antibodies following non-emulsive formulation immunization recognized membrane EGFR; avoid EGF and TGFα coupling to EGFR leading to a marked abrogation of EGFR phosphorylation levels. Non-emulsive formulation also arrests cell cycle in G₀/G₁ stage, demonstrating it preserves previous formulation quality in a newer and simpler formulation.

Open Access Article

Transferability of dermal temperature histamine sensitization test for estimation of pertussis toxin activity in vaccines

Rose Gaines-Das, Masaki Ochiai, Alex Douglas-Bardsley, Cathy Asokanathan, Yoshi Horiuchi, Peter Rigsby, Michael J. Corbel and Dorothy K.L. Xing
Pages 166 - 171
http://dx.doi.org/10.4161/hv.5.3.6615
Abstract | PDF

All current acellular pertussis vaccines (ACVs) contain detoxified pertussis toxin (PT) as a major component. An essential part of the safety evaluation of these vaccines, required by regulatory authorities, is to monitor their active PT content and to check for reversion to toxicity of the detoxified PT. Although various in vitro tests are under investigation, the only practicable means for detecting active PT at present is the histamine sensitization test. The methods given in the European Pharmacopoeia and in the US Pharmacopoeia are based on recording a binary response to histamine challenge (using a lethal end point). A more sensitive method based on measurement of rectal temperature is given in the Japanese Minimum Requirements for Biological Products. More recently, a refinement of this method based on dermal temperature measurement has been developed for ACVs in combination with diphtheria and tetanus vaccines (DTaP). We show that this method also can be used for more complex combination vaccines and is readily transferable. Furthermore use of dermal temperature provides a more precise quantitative estimate of toxin activity than the binary response, leading to an increase in information from a specified number of animals, or allowing a reduction in the number of animals required. We suggest that, pending the development of an alternative in vitro replacement method, the temperature based method may serve as an intermediate solution to the estimation of PT activity giving a precise estimate with reduction in animal numbers.

Open Access Article

Monitoring the rate of hospitalization before rotavirus immunization in Italy utilizing ICD9-CM regional databases

Marchetti Federico, Assael Barouk, Gabutti Giovanni, Guarino Alfredo, Lopalco Pier Luigi, Marocco Alessia, Ruggeri Franco, Titone Lucina, Tozzi Alberto, Vitali Rosati Giovanni, Zotti Carla and Franco Elisabetta
Pages 172 - 176
http://dx.doi.org/10.4161/hv.5.3.6764
Abstract | PDF

Background: Recently, two Rotavirus (RV) vaccines were licensed in Italy, rendering RV illness a vaccine preventable disease. To assess the RV hospitalization rate in Italy, a study focused on the Regional hospital discharge forms (HDD) databases was carried out.

Patients and Methods: Regional HDD databases with the diagnosis of viral enteritis (VE) and RV enteritis (RVE) (ICD9-CM code 00861-69 and 008.8) in any position of the first 20 discharge diagnoses in children aged less or equal to 5 years between 2001 and 2005 were requested.

Results: Regional HDD databases from Piemonte, Veneto, Friuli-Venezia-Giulia, and Marche were analyzed. A total of 434,335 hospitalizations were counted in the study timeframe and 13,234 VE diagnoses (3% of hospitalizations) were collected. A total of 8546 RVE cases (2% of hospitalizations, 64% of all VE) were observed, of which 1.2% were primary diagnoses (PD) and 0.8% secondary diagnosis (SD). The RVE hospitalization peak (4.9 %) was observed at the age of 1 year (4.5% in 7-12 months of age) with a median hospital stay of 4.4 days (s.d ± 4.2). Two deaths (out of 8546 RVE cases) were identified.

Conclusion: Despite some limitations due to the HDD synthetic contents and low potential for clinical interpretation, the Regional HDD databases, including PD and SD, may be a useful tool for monitoring the clinical impact of RV vaccination introduction in Italy.

Open Access Article

General practitioners’ perceptions on pneumococcal vaccination for children in United Kingdom

Anandagiri Shankar, Ravishankar Samraj, Victor Aiyedun, Mandeep Janda and Sam Ramaiah
Pages 177 - 180
http://dx.doi.org/10.4161/hv.5.3.7296
Abstract | PDF

Following the introduction of the pneumococcal conjugate vaccination programme for children in the UK, a study of General Practitioners in Walsall and Liverpool was undertaken to identify the possible reasons for the delay in implementation of the programme. A total of 143 GPs were contacted, of whom 39 responded (response rate =27%). One-third of the GPs felt that there was ‘delay’ in the introduction of the programme. The main reasons for possible delay in the implementation of the programme were ‘problems with databases’, ‘inadequate/unclear information from Primary Care Trust’, ‘lack of public awareness’, and ‘parental delay’. 12% of the respondents said that issue of ‘payment’ to them was the reason for not implementing the programme. Most of the reasons given were ‘external’ to the practitioners. This being an initial exploratory study of its kind, the authors recommend that the results of this study be used in conjunction with other quantitative data by commissioners of health services in designing the implementation of a new vaccination programme.




COMMENTARIES

Open Access Article

Carrier protein conjugate vaccines: The “missing link” to improved antibody and CTL responses?

John M. Timmerman
Pages 181 - 183
http://dx.doi.org/10.4161/hv.5.3.7476
Abstract | PDF

There’s still plenty “missing” from attempts to immunize against cancer and other pesky pathogens.  Conjugation of weakly-immunogenic tumor-derived proteins or other pathogen-associated antigens to highly-immunogenic carrier proteins has long been utilized as a tool for improving immune responses.  Such vaccines have recently been tested in phase 3 clinical trials targeting non-Hodgkin’s B cell lymphoma.  However, these vaccines, composed of tumor-specific immunoglobulin (“idiotype”) protein linked to keyhole limpet hemocyanin using glutaraldehyde, largely failed to show efficacy.  Yet substituting a sulfhydryl-based linker cleavable in lysosomes markedly augments the efficacy of these vaccines, offering heightened antibody and CTL responses.  Could such conjugation strategies be the “missing link” needed in vaccines against pathogens requiring both antibodies and T cells for protection?

Open Access Article

The anthrax vaccine: No new tricks for an old dog

Diane R. Bienek, Lawrence J. Loomis and Raymond E. Biagini
Pages 184 - 189
http://dx.doi.org/10.4161/hv.5.3.7308
Abstract | PDF

The original license for production of the anthrax vaccine, Anthrax Vaccine Adsorbed (AVA), was issued in 1970.  Since that time, over 8 million AVA immunizations have been administered to 2+ million individuals.  In 2002, the National Academy of Sciences, Institute of Medicine, reviewed the safety and efficacy of AVA.  They concluded that the vaccine is acceptably safe and effective in protecting humans against anthrax. The vaccine should protect people against all known strains of anthrax bacteria, as well as against any strains that might be created by potential terrorists or others.  Although the Institute of Medicine concluded that AVA was reasonably safe, they noted that it is fairly common for people to experience local reactions (e.g., redness and swelling at the injection site) and for a smaller number to experience systemic reactions such as fever and malaise, within hours or days of vaccination.  Results of animal studies done previously and subsequent to this report are generally in agreement.  For instance, AVA vaccination increases the level of anthrax anti-protective antigen IgG (anti-PA IgG), which is thought to be one possible correlate of protection (although absolute protective concentrations have not been identified in humans). Anthrax lethal factor neutralization has also been identified as possibly being an important additional correlate of immunity.  Future vaccine research efforts include developing a recombinant anthrax vaccine and anthrax monoclonal antibodies to block the anthrax toxin(s).  It is projected that the next-generation vaccine will elicit a markedly increased anti-anthrax immune response within a shorter time period and consequently, will enable the easier inoculations of individuals working within high-risk areas.